Human milk has long been recognized as the ideal feeding for term infants because of its nutritional composition and immunologic benefits. For these reasons, mature donor human milk was considered a desirable feeding for preterm, low-birth-weight (LBW) infants in early newborn intensive care units (NICUs). However, mature donor milk was found not to provide enough of some nutrients to meet rapidly growing LBW infants' needs. There were also concerns about possible bacterial, viral and other contamination of donor milk. For these reasons, milk from the premature infant's own mother has become the preferred feeding in the modern NICU.
Preterm infants are commonly fed either a commercial infant formula designed specifically for these infants or their own mother's milk. Research is still underway regarding the nutritional requirements of these infants. However, numerous studies have documented that unsupplemented preterm milk and banked term milk provide inadequate quantities of several nutrients to meet the needs of these infants (Davies, D. P., "Adequacy of expressed breast milk for early growth of preterm infants". ARCHIVES OF DISEASE IN CHILDHOOD, 52, p. 296-301, 1997). Estimated energy requirements of the growing LBW infant are approximately 120 Cal/kg/day. Exact energy needs vary among infants because of differences in activity, basal energy expenditure, the efficiency of nutrient absorption, illness and the ability to utilize energy for tissue synthesis. At 120 Cal/kg/day, about 50% of the energy intake of an LBW infant is expended for basal metabolic needs, activity and maintenance of body temperature. About 12.5% is used to synthesize new tissue, and 25% is stored. The remaining 12.5% is excreted. Mature preterm human milk is estimated to contain about 67 Cal/100 ml. To achieve an intake of 120 Cal/kg/day, a LBW infant needs to consume about 180 ml of preterm milk/kg/day. This feeding volume is often not well tolerated. Volumes of 100 to 150 milkg/day are typically fed. Therefore, to achieve an intake of 120 Cal/kg/day in an acceptable volume, the caloric content of preterm milk must be supplemented.
Additionally, relative to estimates of the infant's requirements, preterm human milk is lacking in calcium, phosphorus and protein. When preterm human milk is fortified with protein and energy, a LBW infant's growth approaches that occurring in utero. Additionally, when fortified with calcium and phosphorus, there is increase accretion of these minerals and improvement of bone density. Thus, it has been recommended that when preterm infants are fed preterm human milk, the human milk be fortified to better meet the nutritional needs of the preterm infant.
Liquid and powder forms of preterm milk fortifiers have been marketed domestically in response to this recognized need. The energy and nutrient composition for a typical days supplement of commercially available powder and liquid human milk fortifiers are presented in Table 1.
TABLE 1 Energy and Nutrient Composition of Human Milk Fortifiers Enfamil .RTM. Human Similac Natural Milk Fortifier Care .RTM. Liquid Nutrients Powder (3.8 g) (100 ml) Energy, Kcal 14 81 Protein, gm 0.7 2.2 source whey protein nonfat milk, whey concentrate, protein sodium caseinate concentrate Fat, gm &lt;0.1 4.4 source none added MCT, soy, coconut Carbohydrate, gm 2.7 8.6 source corn syrup solids corn syrup solids, lactose Minerals calcium, mg 90 171 phosphorus, mg 45 94 magnesium, mg 1 10 zinc, mg 0.71 1.22 manganese, mcg 4.7 9.8 copper, mg 0.06 0.2 sodium, mg 7 35 potassium, mg 15.6 105 chloride, mg 17.7 66 iron, mg none added 0.3 selenium, mcg none added 1.46 Vitamins A, IU 950 1,008 D, IU 210 122 E, IU 4.6 3.2 K, mcg 4.4 10 Thiamin, mg 0.15 0.2 Riboflavin, mg 0.21 0.5 B6, mg 0.11 0.2 B12, mcg 0.18 0.45 Niacin, mg 3 4 Folic acid, mcg 25 30 Pantothenic acid, mg 0.73 1.54 Biotin, mcg 2.7 30 C, mg 11.6 30 Enfamil .RTM. Human Milk Fortifier (Mead Johnson Nutritionals, Evansville, Ind.) Values are label claim for 4 packets which is added to 100 ml of mother's milk. Similac Natural Care .RTM. (Ross Products Division of Abbott Laboratories, Chicago, ILL.) Values are label claim for 100 ml.
Similac Natural Care.RTM. and Enfamil.RTM. Human Milk Fortifier are commercially available human milk fortifiers. The fortifiers differ with respect to their form, source of ingredients and energy and nutrient composition. There is need in the NICU for both liquid and powdered human milk fortifiers. Powder products are advantageous to minimize the dilution of mother's milk. For example, dilution of mother's milk is undesirable when a mom is able to produce and pump sufficient milk to meet the volume needs of her infant, However, if mom's milk supply is limited, a liquid fortifier may be used to stretch her supply of human milk. Similac Natural Care.RTM. is designed to be added to preterm milk in a one-to-one ratio or fed alternately with human milk meeting a need in the NICU.
Generally, premature infants stay in the NICU for several weeks after their mother has been released from the hospital. These tiny infants can easily be held in the palm of an adult hand. They are usually placed in special incubators; they are on respirators to assist in their breathing; they have several indwelling catheters for administration and/or withdrawal of fluid samples; and are intubated for tube feeding.
The method of enteral feeding chosen for each infant is based on gestational age, birth weight, clinical condition and experience of the hospital nursing personnel. Specific feeding decisions that are made by the clinician include age to initiate feeding, route of feeding delivery, feeding frequency, strength of feeding, and rate of advancement. The route for enteral feeding is determined by the infant's ability to coordinate sucking, swallowing, and breathing, which appear at approximately 32 to 34 weeks' gestation. Preterm infants of this gestational age who are alert and vigorous may be fed by nipple. Infants who are less mature, weak, or critically ill require feeding by tube to avoid the risk of aspiration and to conserve energy. Nasogastric and orogastric feedings, the most commonly used tube feedings in the neonatal intensive care unit, may be accomplished with bolus or continuous infusions of fortified human milk. Infants who receive nasogastric or orogastric feedings may be fed on an intermittent bolus or continuous schedule. Intermittent feedings every 2 to 3 hours simulate the pattern of feeding the infant will have when advanced to bottle feeding or breast feeding. Continuous feedings may be better tolerated by very small infants, infants who previously have not tolerated bolus feedings and infants in whom clinically significant malabsorption develops with bolus feedings. However, reduced nutrient delivery is a problem associated with continuous feeding. Fat from human milk tends to adhere to the feeding tube surfaces and reduce energy density. Likewise, the loss of nutrients for fortifiers used to supplement human milk is increased when given in a continuous feeding.
In order to continue feeding the infants their own mother's milk after their mother's discharge from the hospital, the mother must express milk at home into suitable containers, store the milk in the refrigerator or freezer and transport the expressed milk to the NICU. Once at the NICU, the milk is stored in refrigerator or freezer temperatures depending on the milk volume required for feeding that day. Typically, the amount of milk that will be fed to the infant within 24 hours after being expressed is refrigerated. The extra expressed milk is frozen. Consequently, the expressed milk may be subjected to several different storage conditions prior to preparation as a days feeding.
Human milk fortification is generally used for all infants who require tube feeding of human milk and for a few infants who require fluid restriction. Typical feeding protocols for premature infants (&lt;1500 g) include the addition of fortifier once the infant is receiving unfortified human milk at approximately 100 ml/kg/day. The fortifier is added at half dose initially. For example, two 0.96 gm packets of Enfamil.RTM. Human Milk Fortifier is added to 100 ml of mother's milk. If the infant tolerates the fortified milk for 24 hours, the fortifier is increased to full dose. In the case of the example above, the fortifier is increased to four 0.96 gm packets in 100 ml of mother's milk.
Typically, the amount of human milk prepared is based on the amount of milk needed to provide the infant with a 24-hour supply. For example, a 1500 gm infant would be fed 150 ml of milk a day. If frozen milk is used, the frozen milk is placed in a warm water bath until completely thawed. Special attention is given to mixing in the fortifiers. Gentle mixing is required to avoid breaking the milk fat globule, which can increase the adherence of the milk fat to the sides of feeding containers and result in significant loss of fat (energy). The prescribed amount of fortified milk is drawn up into syringes and labeled with identification. When milk preparation is complete, the labeled, aliquoted feedings are delivered to the nurseries and placed into refrigerators for easy access by the nursing staff. Typically, the refrigerated fortified milk is warmed prior to feeding. For example, the fortified milk is warmed in a dry heat laboratory incubator set within a range of 35-45.degree. C. for a maximum of 15 minutes. This brings the temperature of the fortified milk to room temperature. The fortified milk may be administered to the infant as a bolus feeding or through a syringe infusion pump for continuous feeding. If an infusion pump is used, the syringe tip is positioned upright to allow for a continuous infusion of fat and the syringe is attached directly to the feeding tube to decrease the potential surface area that the fat and immunologic components may adhere to. The primary advantage of the powdered fortifier is that there is minimal dilution of human milk. There is currently only one powdered human milk fortifier available on the domestic market (Enfamil.RTM. Human Milk Fortifier). Four packets of Enfamil.RTM. Human Milk Fortifier powder (0.96 g powder/packet) is added to 100 mL of preterm milk. A study in preterm infants receiving this powdered fortifier demonstrated poor fat absorption (Schanler, "Suitability of human milk for the low-birth weight infant", CLINICS IN PERINATOLOGY, 22, pp. 207-222, 1995). Poor fat absorption negatively impacts the growth in these premature infants. In addition, reports from the NICUs described a residue that clung to the walls of the reconstitution container when the commercially available fortifier powder was added to human milk and there were concerns that the infants were not actually receiving all the nutrients in the fortified milk.
There is a need for a powdered human milk fortifier which is well tolerated by preterm infants and which demonstrates good fat absorption to provide much needed energy to the preterm infant. Additionally, there is a need for a powdered human milk fortifier that reconstitutes well in human milk so that all of the nutrients are actually delivered to the preterm infant. Further, there is a need for a method of preventing the human milk emulsion from breaking and causing the fat to cling to the syringe and feeding tube thereby under delivering much needed energy calories.
The instant invention is a powdered human milk fortifier that promotes the physical stability of the fortified human milk admixture. Further, the powdered human milk fortifier of the instant invention is well tolerated and maximizes the health benefits of human milk while addressing the variability of human milk as a sole source of energy, protein, calcium, phosphorus, sodium and other micronutrients.